By Jennifer Van Brunt


As the end of the year approaches, the FDA is stepping up its pace of reviewing -- and often approving -- new drugs. Especially for new therapeutics coming from the biotechnology sector, this hyperactivity on the regulatory agency's part has resulted in a slew of high-profile events this month. And these follow on the heels of the most active year yet for biotech product approvals in the U.S. -- a year which will record in the end no fewer than 15 new drug approvals for the sector.

November started out with a bang, when the FDA approved Immunex Corp.'s rheumatoid arthritis drug, Enbrel, for marketing. Enbrel, a recombinant, soluble tumor necrosis factor receptor linked to an immunoglobulin molecule (the Fc portion of human IgG1), is the first biological response modifier approved for treating this often crippling autoimmune disease. Specifically, it is indicated for reducing the signs and symptoms of moderate-to-severe rheumatoid arthritis in patients who have an inadequate response to one or more standard antirheumatic drugs. It can also be used in combination with methotrexate in patients who don't respond well to that drug alone. Immunex (NASDAQ:IMNX), based in Seattle, and its marketing partner Wyeth-Ayerst Laboratories, a division of American Home Products Corp. located in Radnor, Pa., launched the drug within days of the FDA's approval.

Shares in Immunex started to climb in price after the FDA approval on Nov. 2, and have continued to rise as the company has released more clinical data. Immunex shares closed at $70.625 on Nov. 2; they were up to $92.00 by the close of trading on Nov. 23.

Immunex demonstrated that Enbrel is also effective in treating juvenile rheumatoid arthritis; moreover, it presented long-term clinical data on the use of Enbrel in adults. Researchers explained that even after two years of continuous use, the product showed good tolerability with no changes in the side-effect profile.

And though analysts who follow the arthritis drug marketplace say that Enbrel is expensive -- about $11,400 per patient annually (each vial is priced at $110; patients need two vials weekly) -- they also say that Immunex is already seeing Medicare reimbursements on a case-by-case basis in some states, meaning that the stiff price tag will not be a significant deterrent.

Also on Nov. 2, the FDA granted marketing approval to RenaGel Capsules for reducing serum phosphorus in patients with end-stage renal disease. The product, developed by GelTex Pharmaceuticals Inc. (NASDAQ:GELX), of Waltham, Mass., and partner Genzyme Corp. (NASDAQ:GENZ), of Cambridge, Mass., is a non-absorbed polymer-based compound that binds to and eliminates phosphorus from the intestinal tract.

The following day, Nov. 3, the FDA granted marketing approval to SangStat Medical Corp.'s (NASDAQ:SANG) oral cyclosporine product, SangCya. Although not a biotech product, this drug has been shown to be bioequivalent to Swiss pharmaceutical giant Novartis AG's Neoral, used to prevent rejection in organ transplants. It fits into SangStat's business strategy of covering all aspects of the transplantation market, and could finally ensure that the 10-year-old Menlo Park, Calif., firm is within reach of profitability.

In October, the FDA also approved Periostat, an orally administered drug for adjunctive therapy in adult periodontitis, developed by CollaGenex Pharmaceuticals Inc., of Newtown, Pa. Periostat, which contains a sub-antibiotic dose of doxycycline and inhibits the production of collagenase, is CollaGenex's (NASDAQ:CGPI) first approved product. It joins Atridox in the periodontal market. This product, developed by Atrix Laboratories Inc. (NASDAQ:ATRX), of Fort Collins, Colo., was approved for marketing in September. It consists of a biodegradable polymer containing a high dose (10 percent) of the same antibiotic, doxycycline.

On Nov. 16, the FDA's Oncologic Drugs Advisory Committee recommended accelerated approval of DepoCyt, an injectable sustained-release formulation of the chemotherapeutic agent cytarabine, for treating neoplastic meningitis arising from lymphomas. Sponsored by DepoTech Corp. and its development and marketing partner Chiron Corp. (NASDAQ:CHIR), of Emeryville, Calif., DepoCyt is delivered by DepoTech's lipid-based encapsulation system, DepoFoam. In response to the news, investors sent the San Diego company's stock (NASDAQ:DEPO) soaring by nearly 75 percent, from $1.718 to $3.00 per share. DepoTech had taken a beating in December 1997, when the same FDA panel refused to recommend approval of the product for treating neoplastic meningitis arising from solid tumors. After that panel meeting, on Dec. 19, DepoTech's stock shed $8.875, to close the day at $4.125.

On the same day, the same FDA advisory committee also recommended approval of Ligand Pharmaceuticals Inc.'s NDA for Panretin Gel. The product, a chemically synthesized version of the vitamin A derivative 9-cis-retinoic acid, was recommended for the topical treatment of skin lesions in patients with AIDS-related Kaposi's sarcoma. Ligand had halted trading in its stock (NASDAQ:LGND) during the panel's deliberations, but after it resumed trading it closed at $10.625, down by $0.625. Investors remained underwhelmed by the good news, for the following day Ligand's stock dropped a few more pennies, closing at $10.50 on Nov. 17.

In October, an FDA advisory committee voted unanimously to recommend approval of Canadian biotech firm BioChem Pharma Inc.'s (NASDAQ:BCHE) drug for treating hepatitis B virus infection. Epivir-HBV, an oral formulation of the same nucleotide analogue that is approved for treating HIV infection (as Epivir, or 3TC), was licensed by BioChem Pharma to Glaxo Wellcome plc, of London.

Also in October, an FDA panel voted that the agency should approve Cypress Bioscience Inc.'s (NASDAQ:CYPB) Prosorba column for treating rheumatoid arthritis in patients who have failed second-line therapy. The device is a disposable filter that uses Protein A to remove circulating immune complexes from a patient's blood. Cypress Bioscience, of San Diego, is seeking an expanded label for this product, which was first approved in 1987 for treating idiopathic thrombocytopenic purpura, an immune-mediated bleeding disorder.

Late on the afternoon of Nov. 20, the FDA told Ergo Science Corp., of Boston, that its NDA for Ergoset Tablets for treating Type II diabetes was not approvable, citing the benefit-to-risk ratio. On Nov. 23, the company's stock (NASDAQ:ERGO) took a nosedive as investors fled and Boston-based SG Cowen Securities Corp. analyst Felicia Reed lowered her rating to neutral from buy. The stock lost 51 percent, or $1.718, to close at $1.656. The company's stock had already crashed in early May, when the FDA's Endocrinologic and Metabolic Drugs Advisory Committee voted not to recommend the product, bromocryptine mesylate, which is an ergot alkaloid that acts as a dopamine-receptor agonist. At that time the stock lost 55 percent, dropping to $6.25 on May 15, down from a $16 to $18 trading range earlier this year.

In October, an FDA advisory panel also voted against recommending Hirulog, a synthetic thrombin inhibitor for use in angioplasty, sponsored by The Medicines Co., of Cambridge, Mass. And the agency sent a not-approvable letter to Anika Therapeutics Inc. (NASDAQ:ANIK), of Woburn, Mass., for its hyaluronic acid-based Orthovisc for treating osteoarthritis of the knee. *